miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

Xu, Hui; Sun, Jing; Shi, Cuijuan; Sun, Cuiyun; Yu, Lin; Zhao, S. J.; Liu, Jing; Xu, Jinling; Li, Huining; An, Tongqing; Zhou, Xuexia; Ren, Linlin; Wang, Qian; Yu, Shizhu

doi:10.1016/j.neulet.2015.01.060

Cited by 32 publications

(27 citation statements)

References 26 publications

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“…In particular, miR-29 has been shown to suppress GBM cell growth in vitro when transfected (Xu et al, 2015) and to connect with lipid metabolism pathways in liver and hepatoma cells (Kurtz et al, 2014; Xu et al, 2016). Thus, we asked the question whether miR-29 is involved in the EGFR signaling-regulated SCAP/SREBP-1 pathway and GBM tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth

Geng

et al. 2016

Cell Reports

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Summary Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a previously unappreciated link between miR-29 and the SCAP/SREBP-1 pathway in glioblastoma (GBM) growth. EGFR signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3′-untranslated regions. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29, and suggests that miR-29 treatment may represent an effective means to target GBM.

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Section: Introductionmentioning

confidence: 99%

Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth

Geng

et al. 2016

Cell Reports

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“…Xu et al reported that downregulation of miR-29a suppressed the malignant behavior of the U87 cell line [19]; however, the expression and function of miR-29a specifically in GSCs has remained unclear. Because GSCs promote glioblastoma recurrence and reduce the effectiveness of treatments, we conducted our experiments in this subpopulation of cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6

Wang

Xue

et al. 2017

Oncotarget

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Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis. MiR-29a directly inhibited the expression of Quaking gene isoform 6 (QKI-6) by binding to its 3′-UTR, and thus inhibited GSC malignant behavior. In addition, Wilms’ tumor 1-associating protein (WTAP) was identified as a downstream target of QKI-6. Overexpression of miR-29a in GSCs inhibited expression of WTAP and suppressed both phosphoinositide 3-kinase/AKT and extracellular signal-related kinase pathways by downregulating QKI-6, thereby inhibiting cell proliferation, migration, and invasion but promoting apoptosis. We have characterized a novel miR-29a/QKI-6/WTAP axis in GSCs, which may provide theoretical support for the treatment of glioblastoma with miR-29a agomirs.

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“…In breast cancer, miR-29b expression is negatively associated with the HER2 sub-type, and its overexpression inhibits breast cancer cell proliferation and induces apoptosis mainly downregulating STAT3 protein levels 43 . Equally, miR-29b expression inhibits glioblastoma cell proliferation, migration, invasion, angiogenesis and stemness maintenance, while promoting apoptosis, by targeting DNMT3A-3B and BCL2L2 44 45 . Similar tumour suppressor activity for miR-29b in colon 46 , lung 47 and ovarian 48 cancer tissues was reported.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that the cellular context determines the oncogenic or the antioncogenic activity of miR-29b, as previously reported for other miRNAs 49 . Interestingly, PATZ1 role in cancer also appears to be cell context-dependent, and in glioblastoma and colon cancer cells, where miR-29b acts as tumour suppressor 44 45 46 , PATZ1 behaves as an oncogene 14 15 .…”

Section: Discussionmentioning

confidence: 99%

PATZ1 is a target of miR-29b that is induced by Ha-Ras oncogene in rat thyroid cells

Vitiello

Valentino

Menna

et al. 2016

Sci Rep

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The regulatory transcriptional factor PATZ1 is constantly downregulated in human thyroid cancer where it acts as a tumour suppressor by targeting p53-dependent genes involved in Epithelial-Mesenchymal Transition and cell migration. The aim of the present work was to elucidate the upstream signalling mechanisms regulating PATZ1 expression in thyroid cancer cells. The bioinformatics search for microRNAs able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-29b since it was found upregulated in rat thyroid differentiated cells transformed by the Ha-Ras oncogene towards a high proliferating and high migratory phenotype resembling that of anaplastic carcinomas. Functional assays confirmed PATZ1 as a target of miR-29b, and, consistently, an inverse correlation between miR-29b and PATZ1 protein levels was found upon induction of Ha-Ras oncogene expression in these cells. Interestingly, restoration of PATZ1 expression in rat thyroid cells stably expressing the Ha-Ras oncogene decreased cell proliferation and migration, indicating a key role of PATZ1 in Ras-driven thyroid transformation. Together, these results suggest a novel mechanism regulating PATZ1 expression based on the upregulation of miR-29b expression induced by Ras oncogene.

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miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

Cited by 32 publications

References 26 publications

Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth

Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth

Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6

PATZ1 is a target of miR-29b that is induced by Ha-Ras oncogene in rat thyroid cells

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